Molecular differences of NLRP3 inflammasome activation in LPS-activated human monocyte-derived macrophage subtypes
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1
University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Department of Physiology, Hungary
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2
University of Debrecen, , Medical and Health Science Center, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Department of Biochemistry and Molecular Biology, Hungary
IL-1beta is a “master” cytokine that has indispensable roles in orchestrating effective innate and adaptive immune responses.
It is produced in an inactive precursor form that is cleaved to active cytokine
by protein complexes called Nlrp3 inflammasomes (1). While our knowledge on the
general mechanisms involved in Nlrp3 inflammasome function and on its regulation
is rapidly increasing, it is also getting clear that the actual outcome of the
activation (like IL-1beta production) strongly depends on the cell type and on
the presence or absence of various intracellular or extracellular modulators (2). Depending
on their localization macrophages can develop into a wide range of phenotypes. Macrophages
differentiated in the presence of GM-CSF (GM-MFs) develop inflammatory
phenotype, while cells differentiated in the presence of M-CSF (M-MFs) possess
anti-inflammatory characteristics and function in wound healing and tissue
repair.
Our results show that following LPS treatment GM-MFs produce high IL-1beta, while M-MFs produce
low IL-1beta with a different time- and concentration kinetics. We found
significant differences in basal and LPS-induced expression of Nlrp3,
procaspase-1 and ASC between the two MF types. We found that LPS-treated GM-MFs
are able to release ATP and produce IL-1beta, while M-MFs require ATP
supplementation for IL-1beta secretion. We have also found expression differences
in the proteins responsible for ATP release, recognition and degradation as
well as in the activation of key signal transduction pathways. Furthermore, we
will show that different nucleosides have strong and differential regulatory
effects of NLRP3 inflammasome function.
Acknowledgements
This work was supported by TÁMOP 4.2.2.A-11/1/KONV-2012-0023 "VÉD-ELEM" grant and UD Faculty of Medicine Research Fund - Bridging Fund.
References
1. Varga A, Budai MM, Milesz S, Bácsi A, Tőzsér J, Benkő S. 1. Ragweed pollen extract intensifies lipopolysaccharide-induced priming of NLRP3 inflammasome in human macrophages. Immunology. (2013) 138(4):392-401. doi: 10.1111/imm.12052.
2. He Y, Franchi L, Núñez G. : 2.TLR agonists stimulate Nlrp3-dependent IL-1β production independently of the purinergic P2X7 receptor in dendritic cells and in vivo. J Immunol (2013) 190(1):334-9. doi: 10.4049/jimmunol.1202737
Keywords:
Inflammasome,
macrophage,
IL-1beta,
Signal Transduction,
P2X7 receptor,
ATP,
Cytokines
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune receptors and signaling
Citation:
Budai
MM,
Danis
J,
Becsei
Á,
Varga
A,
Csernoch
L,
Tőzsér
J and
Benkő
S
(2013). Molecular differences of NLRP3 inflammasome activation in LPS-activated human monocyte-derived macrophage subtypes.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00471
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Received:
16 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Szilvia Benkő, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Department of Physiology, Debrecen, H-4012, Hungary, szbenko@gmail.com